Our laboratory continues to investigate immune complexes and aggregates in the sera and synovial fluids of patients with connective tissue diseases. For the past year we have been perfecting methods to detect these substances and have been using such techniques as cryoprecipitation, ultracentrifugation, column chromatography, and precipitation in agarose with rheumatoid factors and complement. More recently we have attempted to perfect a quantitative method utilizing tanned sheep red cells coated with human rheumatoid factor. In the coming year our focus will be directed to isolation of immune complexes and aggregates by some of the techniques mentioned above. We plan to select sera and synovial fluids that are particularly rich in complexes and by dissociating various components in an acid medium followed by separation on Sephadex columns we hope to be able to analyze the components in some detail. We are particularly anxious to evaluate antigen-antibody ratios, specific antigens, and the role of rheumatoid factor and complement in modifying the complexes. Some isolated materials will be injected into rabbits to try and develop antisera which may give us clues as to specific components of complexes hitherto unrecognized. Work will continue on correlating characteristics of complexes, titer and class of rheumatoid factor complement levels, and antiDNA titers with disease activity in patients with connective tissue diseases.